In Vitro and In Vivo Efficacy of Amphotericin B Combined with Posaconazole against Experimental Disseminated Sporotrichosis

Abstract

We evaluated the combination of posaconazole with amphotericin B in vitro and in a murine model of systemic infections caused by Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. In vitro data demonstrated a synergistic effect, and although posaconazole alone was effective against sporotrichosis, efficacy in terms of survival and burden reduction was increased with the combination. This combination might be an option against disseminated sporotrichosis, especially when itraconazole or amphotericin B at optimal doses are contraindicated.

FIG 1

Effect of posaconazole and amphotericin B on survival of mice infected intravenously with 2 × 10⁷ CFU/animal of S. brasiliensis and S. schenckii. Posaconazole (PSC) was administered at 2.5 and 5 mg/kg (PSC 2.5 and PSC 5, respectively) and amphotericin B at 0.3 mg/kg (AMB 0.3), both alone and in combination. Values are significant (P < 0.05) in comparison to control (a) and AMB 0.3 (b).

FIG 2

Effect of posaconazole and amphotericin B on fungal loads in spleen and liver of mice 12 days after intravenous infection with 2 × 10⁷ CFU/animal of S. brasiliensis and S. schenckii. Posaconazole was administered at 2.5 and 5 mg/kg (PSC 2.5 and PSC 5, respectively) and amphotericin B at 0.3 mg/kg (AMB 0.3), both alone and in combination. In one strain (FMR 8319), posaconazole was also administered at 10 mg/kg (PSC 10) alone and combined with AMB 0.3. Horizontal bars represent the median values. Values are significant (P < 0.05) in comparison to control (a), AMB 0.3 (b), PSC 2.5 (c), PSC 2.5 plus AMB 0.3 (d), and PSC 5 (e).